Triethylamine → N-(3,4,5-Trimethoxyphenyl)-3-(5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazol-4-oyl)aminophenyl Acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-carboxy-5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazole (1.75 g, 5 mmol) in dichloromethane (30 ml) and THF (1 ml) was added oxalyl chloride (0.88 ml, 10 mmol, 2 eq.) under N2, then DMF (3 drops) to initiate the reaction. The reaction was stirred for 2 h, concentrated, and re-dissolved in dichloromethane (50 ml) under N2. A solution of 2-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide (1.59, 5 mmol) in THF (14 ml) was added, cooled to 0° C., and then added triethylamine (0.7 ml, 5 mmol), and stirred for 17 h. Crude reaction was partitioned between ethyl acetate and 1N HCl. The organic layer was washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude material was titrated with diethyl ether (3×) and purified by flash chromatography (silica gel) using 1-10% acetone in dichloromethane to give the title compound (1.67 g, 51%).

Provenance & Evidence